The objectives of the Molecular Mechanisms of Toxicity Training Program are to provide pre-doctoral trainees with a fundamental education in the mechanisms by which environmental exposures induce human disease, integrated with the basic cellular processes upon which environmental agents impact and cause disease. The training program is based on an understanding of biochemistry, physiology, and molecular/cell biology, toxicology courses in mechanisms by which environmental agents induce toxicity, together with the cellular and molecular processes by which the body defends itself against environmental insult. This didactic training is intimately coupled with in-depth laboratory research training. The goal is to prepare the next generation of scientists to address the ever-present environmental challenges to human health by the prevention of disease, either by nutritional or life-style intervention where possible, or by otherwise exploiting human defense systems. The Training Program is based in the Department of Toxicology and Cancer Biology (DTCB), a basic science department in the College of Medicine that grants the Ph.D. in toxicology and provides an administrative and teaching nucleus of 18 Core Faculty. Joint Faculty from the Colleges of Medicine, Pharmacy, and Agriculture enrich the diversity of training opportunities; 26 of these Core and Joint Faculty with strong research programs make up the Training Grant Faculty. This application requests support for 4 pre-doctoral trainees, and is focused on three disease areas that have an environmental basis: Cancer, Cardiovascular Disease and Neurotoxicity/Neurodegenerative Disease. Oxidative stress, DNA damage/repair and metabolomics are mechanistic themes that underlie many of the research programs and provide highly collaborative and multidisciplinary approaches to problems, thereby providing a rich research training environment. The pre-doctoral training program requires a Biomedical Base (18 credits, including Ethics in Scientific Research), a Toxicology Base (12-14 credits), and an Elective identified by the student's Advisory Committee (3 credits). Pre-doctoral trainees will be supported for a maximum of three years, e.g., years 2-4 of doctoral training. Current enrollment in the Toxicology Ph.D. program is 25, including three Underrepresented Minority students. Recent minority graduates have been primarily recruited from the University of Puerto Rico and have been supported by T35 and R25 NIEHS mechanisms that support summer research experiences in Toxicology; this longstanding tradition of a diverse student body continues to attract new minority students to the training program. The University continues to provide strong support for the DTCB in the form of student fellowships, supplementation to this Training Grant, and new faculty lines, space and equipment so that the program has grown vigorously over the last five years, and is anticipated to continue to do so.